Review article

https://doi.org/10.20471/acc.2026.65.02.15

Targeting Mitochondrial Reactive Oxygen Species in Diabetic Kidney Disease: From Pathogenic Pathways to Therapeutic Interventions

Nishant Goutam orcid.org/0000-0002-2732-5230 ; Department of Pharmacology, Laureate Institute of Pharmacy, Kathog, Jawalamukhi-, Kangra, Himachal Pradesh, India
Alka Sharma orcid.org/0000-0001-9140-4083 ; Department of Pharmacognosy, Laureate Institute of Pharmacy, Kathog, Jawalamukhi, Kangra, Himachal Pradesh, India *
Shavinder Kumari ; Department of Pharmacology, Laureate Institute of Pharmacy, Kathog, Jawalamukhi-, Kangra, Himachal Pradesh, India
Simran Rana ; Department of Pharmacology, Laureate Institute of Pharmacy, Kathog, Jawalamukhi-, Kangra, Himachal Pradesh, India
Gaurav Joshi ; Department of Pharmacy Practice (Pharm. D), University Institute of Pharma Sciences (UIPS), Chandigarh University, Gharuan, Mohali, India
Neeraj Joshi ; Internal Medicine, Senior Clinical Fellow Cardiology, Queen Elizabeth, The Queen Mother Hospital, East Kent University Hospital, Margate, Kent, England

* Corresponding author.

Abstract

Diabetic nephropathy (DN) is the primary cause of chronic kidney disease in individuals
with diabetes. Increasing evidence implicates hyperglycemia-induced
mitochondrial dysfunction and overproduction of mitochondrial reactive oxygen
species (mtROS) as significant contributors to diabetic kidney disease (DKD).
This review aimed to elucidate the role of mitochondrial oxidative stress in the
progression of DKD and to assess emerging therapeutic strategies targeting
mitochondria. A comprehensive analysis of both experimental and clinical studies
was conducted, focusing on the mitochondrial mechanisms underlying DKD
and therapeutic approaches, including conventional renoprotective agents and
mitochondria-targeted interventions.
Hyperglycemia enhances electron transport chain activity, leading to excessive
mtROS generation and activation of inflammatory, fibrotic, and apoptotic
signaling pathways. Current therapies, such as SGLT2 inhibitors, RAAS blockade,
and systemic antioxidants, provide partial protection, but do not directly
address mitochondrial oxidative stress. Emerging strategies, including mitochondria-
targeted antioxidants, Nrf2 activators, mitophagy inducers, and
nanoparticle-based delivery systems, have shown promising renoprotective
effects in preclinical and early clinical studies.
Targeting mitochondrial dysfunction represents a promising therapeutic paradigm
for DKD. Future research should prioritize the development of precise
mitochondrial delivery systems, sensitive mitochondrial biomarkers, and rational
combination therapies to enhance clinical translation and patient outcomes.

Keywords

Mitochondrial ROS; Chronic hyperglycemia; Diabetic nephropathy; ETC dysfunction; Antioxidants

Hrčak ID:

347707

URI

https://hrcak.srce.hr/347707

Publication date:

10.6.2026.

Article data in other languages: croatian

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